This research program utilizes the habenulo-interpeduncular nucleus system to investigate synaptic development and synaptic plasticity. The principal model used consists of comparing synaptic structure and function in normal rats with synaptic structure and function as they develop after a neonatal habenular lesion. Structure will be demonstrated by Golgi and autoradiographic transport methods, at light and electron microscopic levels, by electron microscopic degeneration after a second lesion in the adult, and by freeze-fracture microscopy. Function will be assessed by measurement of 2-deoxyglucose uptake in parallel experiments with neonatal lesions, and as modified by physiological and pharmacological manipulations appropriate to influence activity in this system. Structure and function will be correlated by comparing their respective extent and time course of plasticity after lesions. Study of this system in salamanders by some of these same methods will allow comparison of similarities or differences in plasticity in Amphibia and Mammals. This will enhance insight into the principles of plasticity, utilizing a system which is favorable for comparison because of similar structures in both Classes, as well as assisting future extrapolation to Primates. These studies, building on the considerable body of available data concerning the interpeduncular nucleus, will provide detailed analysis of plasticity in this system. The functional-anatomical correlation will help to clarify the adaptive significance of sprouted synapses. Recognition of factors which influence function will result from the proposed experiments. This will permit the subsequent utilization of this system as a model for studying the effects of external agents as modifiers of the altered development. Such external agents whether drugs or physiological maneuvers are analogous to treatment. Extrapolation will allow development of treatment strategies in the more distant future to improve the outcome of brain and spinal injury in patients. This predictable future clinical application, plus the increase in basic understanding of the process of plasticity and additional insight into its control, are the goals of this project.